pH is a key parameter for many biological processes and also an important indicator for disease progression. For example, endocytosis, a process wherein substances are engulfed by cells, is involved with a pH change from neutral to acidic (pH 4.5-6.2). Due to the Warburg effect, the acidic pH is also characteristic of solid tumors (extracellular pH 6.0-7.0). Therefore, pH-responsive materials such as organic dye-based indicators, cationic polymers, and some peptides often serve as either tools in the fundamental understanding of cell biology or medicine for disease diagnosis and therapy. Nanoparticles often show broad and tunable optical, magnetic, electrical, photothermal properties, and a large surface-to-volume ratio, which allows the integration of different functional groups into one single entity. Therefore, nanoparticles showing pH-dependent interactions with live cells provide new multifunctional tools for disease diagnosis and therapy.
While metal nanoparticles hold great promise in bio-imaging, drug/gene delivery, and phototherapy, their interactions with the cell membrane are generally insensitive to extracellular pH changes in a native biological environment because serum proteins are often adsorbed onto the metal nanoparticles and form a protein “corona”. This protein corona, rather than surface ligands, governs interactions between nanoparticles and the cell membrane. Over 3700 proteins in the serum/plasma and their dynamic adsorption/desorption with the particles create great uncertainties in the rational manipulation of the nanoparticle-cell membrane interactions at different pHs.
Thus, it would be beneficial to create nanoparticles that are capable of interacting with cell membranes in different ways at different pHs, which in turn would allow the advantages of nanoparticle in bioimaging to be extended to many pH dependent biological processes. To address this challenge, the claimed invention comprises metal nanoparticles having little interaction with serum proteins while exhibiting pH-dependent adsorption onto live cell membranes. This simple surface chemical modification, where pH-dependent membrane adsorption is enabled, lends itself to biomedical applications of metal nanoparticles in the fundamental understanding of biological processes as well as disease diagnosis and therapy. The invention was made in part with support under Grant No. RP120588 awarded by the Cancer Prevention and Research Institute of Texas.